Previous studies have demonstrated the presence in plasma and serum of two inhibitors of platelet adhesion to artificial surfaces. One of these inhibitors was shown to be beta-lipoprotein. The second appears to be a macromolecular complex of albumin and immunoglobulin G. We propose to extend these studies in order to further identify and characterize inhibitors of platelet and leukocyte adhesion that are present in plasma. We have preliminary evidence that at least one additional inhibitor is present in plasma. We propose to characterize further the inhibitor that is a macromolecular complex of albumin and immunoglobulin G and to develop methods for quantitating this inhibitor in plasma. The macromolecular complex can be quantitated by radioimmunoassay when it is obtained in highly purified form. Studies will be carried out to determine the mechanism of action of beta-lipoprotein, the macromolecular complex of albumin and immunoglobulin G, and other inhibitors. These studies will be designed to determine whether the inhibitors react with artificial surfaces, with platelets, or with both surfaces and cells. Studies will be extended from consideration only of platelet adhesion to consideration of adhesion of platelets and leukocytes. A small series of different artificial surfaces that have been carefully characterized will be studied for the effects of the various purified inhibitors on adhesion to them of platelets and leukocytes. In addition to the work mentioned above, we plan to carry out three additional studies. In one study we shall determine whether there is a decrease in the levels of the various inhibitors of cell adhesion in the blood of patients before and after hemodialysis. This study could indicate whether inhibitors are lost during exposure of blood to large areas of artificial surfaces. In another study we shall seek to determine whether human endothelial cells in tissue culture produce or degrade any of the plasmatic inhibitors of cell adhesion. Finally, we propose to investigate and compare plasmatic inhibitors of platelet and leukocyte adhesion in cow, sheep, dog, and baboon with those of humans. These studies are to be carried out in an effort to obtain a better understanding of the naturally occurring inhibitors of cell adhesion in plasma and of how they may affect the reaction of blood cells with artificial surfaces. These studies could permit the future use of isolated inhib (Text Truncated - Exceeds Capacity)